Cell type specificity is a property often shared by agents known to both cause cancer and to cure cancer. Understanding the biology of this target cell specificity may allow us to unravel the carcinogenic process to a point where we can rationally and effectively intervene. This may also facilitate the rational design and development of novel cancer chemotherapeutic agents. We have undertaken a multidirectional approach to carcinogenesis and chemotherapy which involves studies on the cell biology of normal and malignant tissues from both humans and rodents. We have demonstrated that certain human lung cancer cell lines, both of the small cell lung cancer (SCLC) and the non-small cell lung cancer (NSCLC) types, retain the ultrastructural and biochemical characteristics of specific cell types present in the lung in vivo. These cell lines have been characterized extensively and have served as model systems to study many diverse but clinically relevant aspects of human lung cancer cell biology. These cell lines have been utilized in collaborative studies on the mechanisms of actions of several chemotherapeutic agents including arabinosyl-5-azacytosine, merbarone, 2', 3'-dideoxycytidine, and BCNU. A well characterized rat alveolar type II cell system has also been developed to study the effects of toxins, carcinogens and anticancer drugs on normal lung cells. Liver cancer cell biology studies which involved chemical transformation of normal rat liver epithelial cells have demonstrated for the first time that there exists a clonal relationship between the two most prominent types of liver cancer, namely hepatocellular carcinomas and cholangiocarcinomas. These studies may lead to the elucidation of the cell types responsible for liver cancer and to more effective therapy. Moreover, the in vitro hepatocarcinogenesis studies have revealed that malignant transformation of rat liver epithelial cells results in the loss of proliferative control exerted by two endogenous polypeptide growth factors, hepatic proliferation inhibitor and transforming growth factor Beta.